A rapid microwave-assisted procedure for easy access to Nx polydentate ligands for potential application in α-RIT

International audienceHeterocycles bearing a hydrazine moiety react with bisaldehydes or bisketones to afford new Nx polydentate ligands suitable for α-radioimmunotherapy. We developed a fast and efficient method using microwave-assisted technology to obtain chelators with variable size and number of coordination centres which were fully characterized. The complexation efficiency with astatine will be assessed

Production/maintenance cooperative scheduling using multi-agents and fuzzy logic

Within companies, production is directly concerned with the manufacturing schedule, but other services like sales, maintenance, purchasing or workforce management should also have an influence on this schedule. These services often have together a hierarchical relationship, i.e. the leading function (most of the time sales or production) generates constraints defining the framework within which the other functions have to satisfy their own objectives. We show how the multi-agent paradigm, often used in scheduling for its ability to distribute decision-making, can also provide a framework for making several functions cooperate in the schedule performance. Production and maintenance have been chosen as an example: having common resources (the machines), their activities are actually often conflicting. We show how to use a fuzzy logic in order to model the temporal degrees of freedom of the two functions, and show that this approach may allow one to obtain a schedule that provides a better compromise between the satisfaction of the respective objectives of the two functions

Are available models reliable for predicting the FRP contribution to the shear resistance of RC beams

In this paper the trustworthiness of the existing theory for predicting the FRP contribution to the shear resistance of reinforced concrete beams is discussed. The most well-known shear models for EBR (External Bonded Reinforcement) are presented, commented on and compared with an extensive experimental database. The database contains the results from more than 200 tests performed in different research institutions across the world. The results of the comparison are not very promising and the use of the additional principle in the actual shear design equations should be questioned. The large scatter between the predicted values of different models and experimental results is of real concern bearing in mind that some of the models are used in present design codes

Antisense oligonucleotides and all-trans retinoic acid have a synergistic anti-tumor effect on oral squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Antisense oligonucleotides against hTR (As-ODN-hTR) have shown promising results as treatment strategies for various human malignancies. All-trans retinoic acid (ATRA) is a signalling molecule with important roles in differentiation and apoptosis. Biological responses to ATRA are currently used therapeutically in various human cancers. The aim of this study was to evaluate the anti-tumor effects of As-ODN-hTR combined with ATRA in vivo.</p> <p>Methods</p> <p>In situ human oral squamous cell carcinoma (OSCC) models were established by subcutaneous injection of Tca8113 cells. Mice were treated with sense oligonucleotides against hTR(S-ODN-hTR) alone, As-ODN-hTR alone, ATRA alone, As-ODN-hTR plus ATRA, or S-ODN-hTR plus ATRA. Tumor size and weight were assessed in the mice. Telomerase activity was detected by a TRAP assay, apoptotic cells were evaluated with a Tunel assay, the expression of apoptosis-related proteins (Bcl-2 and Bax) was evaluated by immunohistochemistry and ultrastructural morphological changes in the tumor specimen were examined.</p> <p>Results</p> <p>Both As-ODN-hTR and ATRA can significantly inhibit tumor growth in this OSCC xenograft solid-tumor model, and the combination of the two agents had a synergistic anti-tumorogenic effect. We also demonstrated that this anti-tumor effect correlated with inhibition of telomerase activity. Furthermore, significant increases in the number of apoptotic cells, typical apoptotic morphology and a downregulation of the anti-apoptotic protein, bcl-2 were observed in the treated tissues.</p> <p>Conclusion</p> <p>The combination of As-ODN-hTR and ATRA has a synergistic anti-tumor effect. This anti-tumor effect can be mainly attributed to apoptosis induced by a decrease in telomerase activity. Bcl-2 plays an important role in this process. Therefore, combining As-ODN-hTR and ATRA may be an approach for the treatment of human oral squamous cell carcinoma.</p

Recent advances in radiotherapy

Radiation therapy has come a long way from treatment planning based on orthogonal radiographs with large margins around tumours. Advances in imaging and radiation planning software have led to three-dimensional conformal radiotherapy and, further, to intensity modulated radiotherapy (IMRT). IMRT permits sparing of normal tissues and hence dose-escalation to tumours. IMRT is the current standard in treatment of head and prostate cancer and is being investigated in other tumour sites. Exquisitely sculpted dose distributions (increased geographical miss) with IMRT, plus tumour motion and anatomical changes during radiotherapy make image guided radiotherapy an essential part of modern radiation delivery. Various hardware and software tools are under investigation for optimal IGRT

IGL-1 solution reduces endoplasmic reticulum stress and apoptosis in rat liver transplantation

Injury due to cold ischemia reperfusion (I/R) is a major cause of primary graft non-function following liver transplantation. We postulated that I/R-induced cellular damage during liver transplantation might affect the secretory pathway, particularly at the endoplasmic reticulum (ER). We examined the involvement of ER stress in organ preservation, and compared cold storage in University of Wisconsin (UW) solution and in Institute Georges Lopez-1 (IGL-1) solution. In one group of rats, livers were preserved in UW solution for 8 h at 4 °C, and then orthotopic liver transplantation was performed according to Kamada's cuff technique. In another group, livers were preserved in IGL-1 solution. The effect of each preservation solution on the induction of ER stress, hepatic injury, mitochondrial damage and cell death was evaluated. As expected, we found increased ER stress after liver transplantation. IGL-1 solution significantly attenuated ER damage by reducing the activation of three pathways of unfolded protein response and their effector molecules caspase-12, C/EBP homologous protein-10, X-box-binding protein 1, tumor necrosis factor-associated factor 2 and eukaryotic translation initiation factor 2. This attenuation of ER stress was associated with a reduction in hepatic injury and cell death. Our results show that IGL-1 solution may be a useful means to circumvent excessive ER stress reactions associated with liver transplantation, and may optimize graft quality